The Association between Type of Insurance Plan, Out-of-Pocket Cost, and Adherence to Antihypertensive Medications in Medicare Supplement Insurance Enrollees.

BACKGROUND: Medicare supplement insurance, or Medigap, covers 21% of Medicare beneficiaries. Despite offsetting some out-of-pocket (OOP) expenses, remaining OOP costs may pose a barrier to medication adherence. This study aims to evaluate how OOP costs and insurance plan types influence medication adherence among beneficiaries covered by Medicare Supplement plans. METHODS: We conducted a retrospective analysis of the MerativeTM MarketScan® Medicare Supplement Database (2017-2019) in Medigap enrollees (≥ 65 years) with hypertension. Proportion of days covered (PDC) was a continuous measure of medication adherence and was also dichotomized (PDC ≥ 0.8) to quantify adequate adherence. Beta-binomial and logistic regression models were used to estimate associations between these outcomes and insurance plan type and log-transformed OOP costs, adjusting for patient characteristics. RESULTS: Among 27,407 patients with hypertension, the average PDC was 0.68 ± 0.31; 47.5% achieved adequate adherence. A mean $1 higher in 30-day OOP costs was associated with a 0.06 (95% Confidence intervals [CI]: -0.09 - -0.03) lower probability of adequate adherence, or a 5% (95% C.I.: 4% - 7%) decrease in PDC. Compared to comprehensive plan enrollees, the odds of adequate adherence were lower among those with point-of-service plans (O.R.: 0.69, 95%C.I.: 0.62 - 0.77), but higher among those with preferred provider organization (PPO) plans (O.R.: 1.08, 95%C.I.: 1.01 - 1.15). Moreover, the association between OOP costs and PDC was significantly greater for PPO enrollees. CONCLUSIONS: While Medicare supplement insurance alleviates some OOP costs, different insurance plans and remaining OOP costs influence medication adherence. Reducing patient cost-sharing may improve medication adherence.

Preclinical development of EXT608, an investigational parathyroid hormone derivative with extended half-life for the treatment of hypoparathyroidism.

Hypoparathyroidism, a deficiency of parathyroid hormone (PTH), results in hypocalcemia, hyperphosphatemia, and hypercalciuria. The disease is poorly controlled by calcium and vitamin D supplements or native PTH(1-84) replacement therapy. A version of PTH is being developed using D-VITylation technology, whereby vitamin D is conjugated to a therapeutic peptide, which confers a long plasma half-life by virtue of binding to the abundant vitamin D binding protein (DBP). D-VITylation of PTH caused no reduction in activity at the PTHR1 receptor, and resulted in a plasma elimination half-life of 7-15 h in rats and 24-32 h in cynomolgus monkeys. Analysis of steady-state pharmacokinetics as a function of dose showed flat profiles with smaller peak:trough ratios at low doses, indicative of slower subcutaneous absorption. In thyroparathyroidectomized (TPTx) rats, PTH(1-34)-vitamin D conjugates restored serum calcium and phosphate levels into the normal range over the 24 h dosing period, and increased bone turnover markers and reduced bone mineral density. Urinary calcium was initially elevated, but normalized by the end of treatment on day 27. In healthy monkeys, a single dose of PTH(1-34)-vitamin D conjugates elevated serum calcium levels above the normal range for a period of 24-48 h while simultaneously reducing urinary calcium. Therefore, the lead compound, EXT608, is a promising candidate as a therapeutic that can truly mimic the endogenous activity of PTH and warrants further study in patients with hypoparathyroidism.

Racial and ethnic differences in patterns of use and discontinuation of long-acting injectable antipsychotics using Medicaid claims data.

Introduction: In general, racial and ethnic differences exist in antipsychotic prescription practices. However, little is known about such differences between individual long-acting injectable (LAI) antipsychotic formulations, specifically. This study's primary objective was to determine racial and ethnic differences among LAI antipsychotic use. Secondary objectives were to identify if discontinuation rates differed between agents and by race or ethnicity. Methods: International Classification of Diseases, 10th edition (ICD-10) codes were used to identify patients with schizophrenia and related disorders (18-64 years) who received an LAI antipsychotic between 2016 and 2020 using Merative Multi-State Medicaid databases. Using National Drug Code numbers for LAI antipsychotics, pharmacy claims were identified and data analyzed. Cochran-Mantel-Haenszel tests and odds ratio estimators were used to investigate conditional association between race or ethnicity and medication, while controlling for age, sex, health plan, and prescription year. Kaplan-Meier survival curves were examined, and stratified log-rank tests were conducted to compare the time until discontinuation distributions by race or ethnicity. Results: The analysis included 37 712 patients. Blacks received an LAI first-generation antipsychotic more often than Whites (OR: 1.64, 95% CI: [1.56, 1.73], Hispanics (OR: 1.46, 95% CI: [1.21, 1.75]) and others (OR: 1.44, 95% CI: [1.20, 1.73]). Aside from fluphenazine decanoate showing earlier discontinuation rates for Whites over Blacks (P = .02), no significant differences in discontinuation across race or ethnicity were identified. Discussion: Despite no significant differences in second-generation antipsychotic LAI discontinuation rates between Blacks and other racial or ethnic groups, Blacks received second-generation antipsychotic LAIs significantly less often than other groups. Further studies are needed to determine why differences may be occurring.

Early growth, development and allometry of glyphosate-resistant and susceptible Amaranthus palmeri in response to current and elevated temperature and CO2.

This study aimed to evaluate the influence of CO2 and temperature on glyphosate-resistant and susceptible biotypes of Amaranthus palmeri (Palmer amaranth) in terms of morphological development. Height (cm), stem diameter (cm), leaf area (cm2), number of leaves, leaf, stem, and root dry matter, plant volume (m3), as well as shoot-to-root allometry were evaluated. The Palmer amaranth biotypes were grown under four different scenarios: 1-low temperature (23/33 °C) and CO2 (410 ± 25 ppm); 2-low temperature (23/33 °C) and high CO2 (750 ± 25 ppm); 3-high temperature (26/36 °C) and low CO2 (410 ± 25 ppm); and 4-high temperature (26/36 °C) and CO2 (750 ± 25 ppm). Between CO2 and temperature, the majority of differences observed were driven by CO2 levels. Palmer amaranth grown under 750 ppm of CO2 was 15.5% taller, displayed 10% more leaf area (cm2), 18% more stem dry matter, and had a 28.4% increase in volume (m3) compared to 410 ppm of CO2. GA2017 and GA2020 were 18% and 15.5% shorter, respectively. The number of leaves was 27% greater for GA2005. Plant volume decreased in GA2017 (35.6%) and GA2020 (23.8%). The shoot-to-root ratio was isomeric, except at 14 and 21 DAT, where an allometric growth towards shoot development was significant. Palmer amaranth biotypes responded differently to elevated CO2, and the impacts of temperature need further investigation on weed physiology. Thus, environmental and genetic background may affect the response of glyphosate-resistant and susceptible populations to climate change scenarios.

EXT418, a novel long-acting ghrelin, mitigates Lewis lung carcinoma induced cachexia in mice.

BACKGROUND: Ghrelin is a potential therapy for cachexia due to its orexigenic properties and anabolic effects on muscle and fat. However, its clinical use is limited by the short half-life of active (acylated) ghrelin (~11 min in humans). EXT418 is a novel long-acting, constitutively active ghrelin analog created by covalently linking it to a vitamin D derivative. Here, we evaluated the effects and mechanisms of action of EXT418 on Lewis lung carcinoma (LLC)-induced cachexia in mice. METHODS: Male C57BL/6J mice (5- to 7-month-old) were implanted with 1 × 106 heat-killed (HK) or live LLC cells. When the tumour was palpable, mice were injected with vehicle (T + V) or EXT418 daily (T + 418 Daily, 0.25 mg/kg/day) or every other day (T + 418 EOD, 0.5 mg/kg/EOD) for up to 14 days, whereas HK-treated mice were given vehicle (HK + V). Subsets of T + 418 Daily or EOD-treated mice were pair-fed to the T + V group. Body composition and grip strength were evaluated before tumour implantation and at the end of the experiment. Molecular markers were probed in muscles upon termination. RESULTS: In tumour-bearing mice, administration of EXT418 daily or EOD partially prevented weight loss (T + V vs. T + 418 Daily, P = 0.030; and vs. T + 418 EOD, P = 0.020). Similar effects were observed in whole body fat and lean body mass. Grip strength in tumour-bearing mice was improved by EXT418 daily (P = 0.010) or EOD (P = 0.008) administration compared with vehicle-treated mice. These effects of EXT418 on weight and grip strength were partially independent of food intake. EXT418 daily administration also improved type IIA (P = 0.015), IIB (P = 0.037) and IIX (P = 0.050) fibre cross-sectional area (CSA) in tibialis anterior (TA) and EXT418 EOD improved CSA of IIB fibres in red gastrocnemius (GAS; P = 0.005). In skeletal muscles, tumour-induced increases in atrogenes Fbxo32 and Trim63 were ameliorated by EXT418 treatments (TA and GAS/plantaris, PL), which were independent of food intake. EXT418 administration decreased expression of the mitophagy marker Bnip3 (GAS/PL; P ≤ 0.010). Similar effects of EXT418 EOD were observed in p62 (GAS/PL; P = 0.039). In addition, EXT418 treatments ameliorated the tumour-induced elevation in muscle Il6 transcript levels (TA and GAS/PL), independently of food intake. Il-6 transcript levels in adipose tissue and circulating IL-10 were elevated in response to the tumour but these increases were not significant with EXT418 administration. Tumour mass was not altered by EXT418. CONCLUSIONS: EXT418 mitigates LLC-induced cachexia by attenuating skeletal muscle inflammation, proteolysis, and mitophagy, without affecting tumour mass and partially independent of food intake.

Utilization of Counseling Services by Pediatric Patients With Obesity Using MarketScan Data (2017-2019).

The United States has implemented policy efforts for public and private insurance to cover counseling services related to the treatment of obesity. However, no research has yet studied counseling service utilization among pediatric patients with obesity. We used 3 years (2017-2019) of IBM MarketScan Commercial Claims and Encounters Database and IBM MarketScan Multi-State Medicaid Data to examine such utilization patterns. We found the proportion of patients receiving any counseling services to be low among both privately insured (7.06%-7.97%) and Medicaid patients (9.51%-11.61%) within 6 months from diagnosis of obesity. This underutilization is concerning as many pediatric patients go undiagnosed, as evidenced in this research. Among the utilized services, nutrition counseling and face-to-face counseling were utilized the most by privately and Medicaid-insured patients over 6- and 12-month follow-ups. Our study underscores the need for implementing policies and programs to promote the utilization of counseling services among pediatric patients.

D-VITylation: Harnessing the biology of vitamin D to improve the pharmacokinetic properties of peptides and small proteins.

Peptides have great potential to be potent and specific therapeutics, yet their small size leads to rapid glomerular filtration, which severely limits therapeutic applications. Although conjugation of small proteins to large polymers typically results in longer residence times, these conjugates often have a significant loss of biological activity due to steric hindrance. Here, we improve the pharmacokinetics (PK) of peptide therapeutics by harnessing the biology of vitamin D. Attachment of a small vitamin D-based molecule (D-VITylation) protects the conjugated peptide or protein from renal clearance by virtue of reversible binding to the serum-circulating vitamin D binding protein (DBP), without compromising bioactivity. Varying the conjugation site on vitamin D affects the binding to DBP, with higher affinity corresponding to a longer plasma half-life. We also demonstrate the important contribution of the peptide to the overall PK, likely due to alternative clearance mechanisms such as protease degradation and receptor-mediated cellular uptake. With a Fab antibody fragment, for which these alternate clearance mechanisms are not significant, D-VITylation increases the half-life of elimination from 14 to 61 h in rats. The PK profile in minipigs and projected lifetime in humans suggest that D-VITylation is a viable strategy to achieve once-weekly dosing of peptide therapeutics in humans.

Vitamin D Supplementation Does Not Impact Insulin Resistance in Black and White Children.

CONTEXT: Vitamin D supplementation trials with diabetes-related outcomes have been conducted almost exclusively in adults and provide equivocal findings. OBJECTIVE: The objective of this study was to determine the dose-response of vitamin D supplementation on fasting glucose, insulin, and a surrogate measure of insulin resistance in white and black children aged 9­13 years, who participated in the Georgia, Purdue, and Indiana University (or GAPI) trial: a 12-week multisite, randomized, triple-masked, dose-response, placebo-controlled vitamin D trial. DESIGN: Black and white children in the early stages of puberty (N = 323, 50% male, 51% black) were equally randomized to receive vitamin D3 (0, 400, 1000, 2000, or 4000 IU/day) for 12 weeks. Fasting serum 25-hydroxyvitamin D (25(OH)D), glucose and insulin were assessed at baseline and weeks 6 and 12. Homeostasis model assessment of insulin resistance was used as a surrogate measure of insulin resistance. Statistical analyses were conducted as intent-to-treat using a mixed effects model. RESULTS: Baseline serum 25(OH)D was inversely associated with insulin (r = −0.140, P = 0.017) and homeostasis model assessment of insulin resistance (r = −0.146, P = 0.012) after adjusting for race, sex, age, pubertal maturation, fat mass, and body mass index. Glucose, insulin, and insulin resistance increased (F > 5.79, P < .003) over the 12 weeks, despite vitamin D dose-dependent increases in serum 25(OH)D. CONCLUSIONS: Despite significant baseline inverse relationships between serum 25(OH)D and measures of insulin resistance, vitamin D supplementation had no impact on fasting glucose, insulin, or a surrogate measure of insulin resistance over 12 weeks in apparently healthy children.

Exposure of pregnant women to cookstove-related household air pollution in urban and periurban Trujillo, Peru.

Although evidence suggests associations between maternal exposure to air pollution and adverse birth outcomes, pregnant women's exposure to household air pollution in developing countries is understudied. Personal exposures of pregnant women (N = 100) in Trujillo, Peru, to air pollutants and their indoor concentrations were measured. The effects of stove-use-related characteristics and ambient air pollution on exposure were determined using mixed-effects models. Significant differences in 48-hour kitchen concentrations of particulate matter (PM2.5), carbon monoxide (CO), and nitrogen dioxide (NO2) concentrations were observed across fuel types (p < 0.05). Geometric mean PM2.5 concentrations where 112 µg/m(3) (confidence limits [CLs]: 52, 242 µg/m(3)) and 42 µg/m(3) (21, 82 µg/m(3)) in homes where wood and gas were used, respectively. PM2.5 exposure was at levels that recent exposure-response analyses suggest may not result in substantial reduction in health risks even in homes where cleaner burning gas stoves were used.

Weight gain in college females is not prevented by isoflavone-rich soy protein: a randomized controlled trial.

Human clinical trials targeted at preventing gains in body weight using soy protein and isoflavones are limited to adults and yield conflicting results. We hypothesized that daily intake of soy protein/isoflavones would attenuate gains in body weight to a greater extent than a casein-based control in 18 to 19 year-old females. To test this hypothesis, we conducted a randomized, double blind, placebo-controlled trial over 16 weeks to examine the effects of a soy protein/isoflavone-based meal replacement (experimental group) versus a casein-based meal replacement (control group) on body weight and body composition variables in female college freshmen (N = 120). Fat mass (FM), fat-free soft tissue mass (FFST), and percent body fat (%BF) were measured using dual energy X-ray absorptiometry (DXA; Delphi A). Repeated measures mixed models were used to determine the effects of treatment on anthropometric and body composition variables (body weight, waist circumference, FM, FFST, and %BF). No significant group×time interactions were observed, even when body mass index was controlled for in the analysis. Over 16 weeks, body weight, FM, FFST, and %BF significantly increased in both groups (P < .05). Our findings show that female college freshmen gained a significant amount of weight over the course of the 16-week study. Gains in body weight and FM were similar among participants assigned to the soy protein/isoflavone- and the casein-based meal replacements. Future research is warranted to determine the effects of soy protein/isoflavone- and casein-based meal replacements versus a non-intervention (i.e., non-protein based) control.

A Pilot Study Characterizing Real Time Exposures to Particulate Matter and Carbon Monoxide from Cookstove Related Woodsmoke in Rural Peru.

Nearly half of the world's population is exposed to household air pollution (HAP) due to long hours spent in close proximity to unvented cooking fires. We aimed to use PM2.5 and CO measurements to characterize exposure to cookstove generated woodsmoke in real time among control (n=10) and intervention (n=9) households in San Marcos, Cajamarca Region, Peru. Real time personal particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5), and personal and kitchen carbon monoxide (CO) samples were taken. Control households used a number of stoves including open fire and chimney stoves while intervention households used study-promoted chimney stoves. Measurements were categorized into lunch (9am - 1pm) and dinner (3pm - 7pm) periods, where applicable, to adjust for a wide range of sampling periods (2.8- 13.1hrs). During the 4-h time periods, mean personal PM2.5 exposures were correlated with personal CO exposures during lunch (r=0.67 p=0.024 n=11) and dinner (r=0.72 p=0.0011 n=17) in all study households. Personal PM2.5 exposures and kitchen CO concentrations were also correlated during lunch (r=0.76 p=0.018 n=9) and dinner (r=0.60 p=0.018 n=15). CO may be a useful indicator of PM during 4-h time scales measured in real time, particularly during high woodsmoke exposures, particularly during residential biomass cooking.

Concentrations of urinary 8-hydroxy-2'-deoxyguanosine and 8-isoprostane in women exposed to woodsmoke in a cookstove intervention study in San Marcos, Peru.

Nearly half of the world's population is exposed to household air pollution (HAP) due to long hours spent in close proximity to unvented cooking fires. The effect of woodsmoke exposure on oxidative stress was examined by investigating the association between woodsmoke exposure and biomarkers of DNA oxidation (8-hydroxy-2'-deoxyguanosine [8-OHdG]) and lipid peroxidation (8-isoprostane) among control and intervention stove users. HAP exposure assessment was conducted within the framework of a community-randomized controlled trial of 51 communities in San Marcos Province, Cajamarca Region, Peru. The first morning urine voids after 48h HAP exposure assessment from a subset of 45 control and 39 intervention stove users were analyzed for 8-OHdG and 8-isoprostane. General linear models and correlation analyses were performed. Urinary oxidative stress biomarkers ranged from 11.2 to 2270.0µg/g creatinine (median: 132.6µg/g creatinine) for 8-OHdG and from 0.1 to 4.5µg/g creatinine (median: 0.8µg/g creatinine) for 8-isoprostane among all study subjects (n=84). After controlling for the effects of traffic in the community and eating food exposed to fire among all subjects, cooking time was weakly, but positively associated with urinary 8-OHdG (r=0.29, p=0.01, n=80). Subjects' real-time personal CO exposures were negatively associated with 8-OHdG, particularly the maximum 30-second CO exposure during the sampling period (r=-0.32, p=0.001, n=73). 48h time integrated personal PM2.5 was negatively, but marginally associated with urinary 8-isoprostane (r=-0.21, p=0.09, n=69) after controlling for the effect of distance of homes to the road. Urinary 8-isoprostane levels reported in the available literature are comparable to results found in the current study. However there were relatively high levels of urinary 8-OHdG compared to data in the available literature for 8-OHdG excretion. Results suggest a sustained systemic oxidative stress among these Peruvian women chronically exposed to wood smoke.

Carbon monoxide exposures and kitchen concentrations from cookstove-related woodsmoke in San Marcos, Peru.

BACKGROUND: Nearly half of the world's population is exposed to household air pollution (HAP) due to long hours spent in close proximity to biomass-fueled fires. OBJECTIVE: We compare CO exposures and concentrations among study promoted intervention stove users and control stove users in San Marcos Province, Cajamarca region, Peru. METHODS: Passive CO diffusion tubes were deployed over a 48-hour sampling period to measure kitchen CO concentrations and personal mother and child CO exposures in 197 control and 182 intervention households. RESULTS: Geometric means (95% CI) for child, mother, and kitchen measurements were 1.1 (0.9-1.2), 1.4 (1.3-1.6), and 7.3 (6.4-8.3) ppm in control households, and 1.0 (0.9-1.1), 1.4 (1.3-1.6), and 7.3 (6.4-8.2) ppm among intervention households, respectively. CONCLUSION: With no significant differences between control and intervention CO measurements, results suggest that intervention stove maintenance may be necessary for long-term reductions in CO exposures.

Concentrations of select persistent organic pollutants across pregnancy trimesters in maternal and in cord serum in Trujillo, Peru.

Although the production and use of some persistent organic pollutants (POPs) have been banned or highly restricted, human exposure remains a subject of investigation due to their environmental persistence. Physiological changes during pregnancy may affect the disposition of POPs in the mother's body, and thus fetal exposure. Changes in serum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) across pregnancy trimesters, and trans-placental transfer to the fetus were investigated. Seventy-nine pregnant women in Trujillo, Peru were recruited in the first trimester of pregnancy, and provided blood samples for the analysis of 35 PCB congeners, 9 OCPs, and 11 polybrominated biphenyl diethers (PBDEs). Subsequently, maternal blood samples were collected in the second (n=64) and third trimesters (n=59), and cord blood samples (n=50) were collected at delivery. There were statistically significant changes across trimesters (p<0.05) for both fresh weight (increase) and lipid adjusted concentrations (decrease) of hexachlorobenzene (HCB), 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE), PCB-74, 118, 138-158, 153, 170, 180 and 194. Fresh weight concentrations of these POPs increased from first to third trimester by 10-28%. On the other hand lipid adjusted concentrations decreased from first to third trimester by 16-28%. Serum lipids increased from first to third trimester by 53% indicating the dilution of the POPs in the lipids. Concentrations of 2,2-Bis(4-chlorophenyl)-1,1,1-trichloroethane (p,p'-DDT), its metabolite p,p'-DDE, PCB-118, 138-158, 153, 170 and 180 above their limits of detection were measured in >60% of cord serum samples. Intra-individual correlations in maternal serum concentrations were high for most of the POPs (ρ=0.62-0.99; p<0.05) while correlations between maternal and cord serum concentrations were also high (ρ=0.68-0.99; p<0.05). Results indicate that the disposition in the body and blood concentrations of POPs may change during pregnancy, and show trans-placental transfer of DDT, DDE and PCBs.

Occupational exposure to woodsmoke and oxidative stress in wildland firefighters.

Experimental studies indicate that exposure to woodsmoke could induce oxidative stress. However studies have not been conducted among the general population and specialized occupational groups despite the existence of elevated woodsmoke exposure situations. Therefore, we investigated whether there were across workshift changes in oxidative stress biomarkers among wildland firefighters who are occupationally exposed to elevated levels of woodsmoke. We collected pre- and post-workshift urine samples from 19 wildland firefighters before and after prescribed burns. We measured malondialdehyde (MDA) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in the samples, and analyzed whether there were cross-shift changes in their levels, and the relationships between the changes and the length of firefighting career, age of firefighter, and quantified workshift exposure to particulate matter. Overall no significant cross-shift change was observed for 8-oxodG or MDA in the urine samples of the firefighters. Changes in both biomarkers were also not associated with PM2.5, which was used as a marker of exposure. However, overall unadjusted geometric mean 8-oxo-dG levels in the samples (31 µg/g creatinine) was relatively higher compared to those measured in healthy individuals in many occupational or general population studies. Additionally, cross-shift changes in 8-oxo-dG excretion were dependent on the length of firefighting career (p=0.01) or age of the subject (p=0.01). Significant increases in 8-oxo-dG level from pre-shift to post-shift were observed for those who had been firefighters for 2 years or less. The results indicate that oxidative stress response measured as cross-shift changes in 8-oxo-dG may depend on age or the length of a firefighter's career. These results suggest the need to investigate the longer term health effects of cumulative exposure of woodsmoke exposure among wildland firefighters, because increased body burden of oxidative stress is a risk factor for many diseases and is theorized to be involved in aging.

Biomonitoring of polycyclic aromatic hydrocarbon exposure in pregnant women in Trujillo, Peru--comparison of different fuel types used for cooking.

Women and children in developing countries are often exposed to high levels of air pollution including polycyclic aromatic hydrocarbons (PAHs), which may negatively impact their health, due to household combustion of biomass fuel for cooking and heating. We compared creatinine adjusted hydroxy-PAH (OH-PAH) concentrations in pregnant women in Trujillo, Peru who cook with wood to levels measured in those who cook with kerosene, liquefied petroleum gas or a combination of fuels. Seventy-nine women were recruited for the study between May and July 2004 in the first trimester of their pregnancy. Urine samples were collected from the subjects in the first, second and third trimesters for OH-PAH analyses. The concentrations of the OH-PAHs were compared across the type of fuel used for cooking and pregnancy trimesters. The relationships between OH-PAHs levels in the first trimester and concurrently measured personal exposures to PM2.5, carbon monoxide and nitrogen dioxide together with their indoor and outdoor air concentrations were also investigated. Women cooking with wood or kerosene had the highest creatinine adjusted OH-PAH concentrations compared with those using gas, coal briquette or a combination of fuels. Concentrations of creatinine adjusted 2-hydroxy-fluorene, 3-hydroxy-fluorene, 1-hydroxy-fluorene, 2-hydroxy-phenanthrene and 4-hydroxy-phenanthrene were significantly higher (p<0.05) in women who used wood or kerosene alone compared with women who used liquefied petroleum gas (LPG), coal briquette or a combination of fuels. An increase in the concentrations of creatinine adjusted 9-hydroxy-fluorene, 1-hydroxy-phenanthrene, 2-hydroxy-phenanthrene, 4-hydroxy-phenanthrene and 1-hydroxy-pyrene in the third trimesters was also observed. Weak positive correlation (Spearman correlation coefficient, ρ<0.4; p<0.05) was observed between all first trimester creatinine adjusted OH-PAHs and indoor (kitchen and living room), and personal 48-h TWA PM2.5. Women who cooked exclusively with wood or kerosene had higher creatinine adjusted OH-PAH levels in their urine samples compared to women who cooked with LPG or coal briquette.

Utility of urinary Clara cell protein (CC16) to demonstrate increased lung epithelial permeability in non-smokers exposed to outdoor secondhand smoke.

The objective of this study was to assess the utility of urinary Clara cell protein (CC16) as a biomarker of increased lung epithelial permeability in non-smokers exposed to outdoor secondhand smoke. Twenty-eight healthy non-smoking adults visited outdoor patios of a restaurant and a bar where non-participants smoked and an open-air control with no smokers on three weekend days in a crossover study; subjects visited each site once for 3 h. Urine samples were collected at baseline, immediately post exposure and next morning, and analyzed for CC16. Changes in CC16 across location types or with cigarette count were analyzed using mixed-effect models, which included all subjects and stratified by gender. Urinary CC16 was higher in males (n=9) compared with females (n=18) at all measurement occasions (P<0.002), possibly reflecting prostatic contamination. Urinary CC16 from pre-exposure to post-exposure was higher following visits to restaurant and bar sites compared with the control among females but this increase did not reach statistical significance. Post-exposure to pre-exposure urinary CC16 ratios among females increased with cigarette count (P=0.048). Exposure-related increases in urinary CC16 were not seen among males. In conclusion, urinary CC16 may be a useful biomarker of increased lung epithelial permeability among female non-smokers; further work will be required to evaluate its applicability to males.

Decision making under time pressure, modeled in a prospect theory framework.

The current research examines the effects of time pressure on decision behavior based on a prospect theory framework. In Experiments 1 and 2, participants estimated certainty equivalents for binary gains-only bets in the presence or absence of time pressure. In Experiment 3, participants assessed comparable bets that were framed as losses. Data were modeled to establish psychological mechanisms underlying decision behavior. In Experiments 1 and 2, time pressure led to increased risk attractiveness, but no significant differences emerged in either probability discriminability or outcome utility. In Experiment 3, time pressure reduced probability discriminability, which was coupled with severe risk-seeking behavior for both conditions in the domain of losses. No significant effects of control over outcomes were observed. Results provide qualified support for theories that suggest increased risk-seeking for gains under time pressure.

Exposure to secondhand smoke outside of a bar and a restaurant and tobacco exposure biomarkers in nonsmokers.

BACKGROUND: With an increase in indoor smoking bans, many smokers smoke outside establishments and near their entrances, which has become a public health concern. OBJECTIVES: We characterized the exposure of nonsmokers to secondhand smoke (SHS) outside a restaurant and bar in Athens, Georgia, where indoor smoking is banned, using salivary cotinine and urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). METHODS: In a crossover study, we assigned 28 participants to outdoor patios of a restaurant and a bar and an open-air site with no smokers on three weekend days; participants visited each site once and stayed for 3 hr. We collected saliva and urine samples immediately before and after the visits (postexposure) and on the following morning and analyzed samples for cotinine and total NNAL, respectively. Regression models were fitted and changes in biomarkers were contrasted between locations. RESULTS: Postexposure and preexposure geometric mean salivary cotinine concentrations differed by 0.115 ng/mL [95% confidence interval (CI): 0.105, 0.126)] and by 0.030 ng/mL (95% CI: 0.028, 0.031) for bar and restaurant visits, respectively. There were no significant post- and preexposure differences in cotinine levels after control site visits, and changes after bar and restaurant site visits were significantly different from changes after control site visits (p < 0.001). Results comparing next-day and preexposure salivary cotinine levels were similar. Next-day creatinine-corrected urinary NNAL concentrations also were higher than preexposure levels following bar and restaurant visits [1.858 pg/mg creatinine higher (95% CI: 0.897, 3.758) and 0.615 pg/mg creatinine higher (95% CI: 0.210, 1.761), respectively], and were significantly different from changes after the control visits (p = 0.005). CONCLUSION: Salivary cotinine and urinary NNAL increased significantly in nonsmokers after outdoor SHS exposure. Our findings indicate that such exposures may increase risks of health effects associated with tobacco carcinogens.

Personal exposure to PM(2.5) and urinary hydroxy-PAH levels in bus drivers exposed to traffic exhaust, in Trujillo, Peru.

Public transport vehicle drivers, especially in highly polluted or trafficked areas, are exposed to high levels of air pollutants. In this study, we assessed the influence of traffic on levels of hydroxy polycyclic aromatic hydrocarbons (OH-PAHs) in commercial bus drivers in Trujillo, Peru, by measuring the within-shift changes in the urinary whole weight and creatinine-corrected concentrations of the PAH metabolites. We measured personal PM(2.5) as a proxy of exposure to traffic emission. Urine samples were collected daily from two bus drivers and three minivan drivers in Trujillo, pre-, mid-, post-work shift and on days when the drivers were off work (total n = 144). Ten OH-PAH metabolites were measured in the urine samples. Drivers were also monitored for exposure to PM(2.5) (n = 41). Daily work shift (mean = 13.1 ± 1.3 hr) integrated PM(2.5) was measured in the breathing zones of the drivers for an average of 10.5 days per driver. The differences across shift in OH-PAH concentrations were not statistically significant except for urinary 2-hydroxyfluorene (2-FLU) (p = 0.04) and 4-hydroxyphenanthrene (4-PHE) (p = 0.01) and creatinine-corrected 4-hydroxyphenanthrene (p = 0.01). Correlation between pairs of hydroxy-PAHs (ρ = 0.50 to 0.93) were highest for mid-shift samples. Concentrations of PM(2.5) (geometric mean = 64 µg/m(3); 95% confidence limits = 52 µg/m(3), 78 µg/m(3)) is similar to those measured in many other studies of traffic exposure. There was significant change across work shift for concentrations of only two of the OH-PAHs (2-FLU and 4-PHE). Results indicate that the drivers may have had limited time for clearance of PAH exposure from the body between work shifts. Comparisons of the concentrations of creatinine-corrected hydroxy-PAH to those reported in other studies indicate that exposure of public transport drivers to PAH could be similar. By following the subjects over multiple days, this study gives an indication of appropriate exposure situations for the use of hydroxy-PAHs and will be beneficial in designing future occupational studies of PAH exposure.